Objectives: Elucidation of mechanisms regulating the hepatobiliary fate of chemical carcinogens and other xenobiotics. Specific Aims: (1) Investigate the role of glutathione (GSH) in the metabolism and biliary excretion of N, N-dimethyl-4-aminoazobenzene (DAB). (2) Identify and characterize cytosolic factors which affect microsomal metabolism of DAB. Methods: (1) Hepatic GSH levels are altered by treating rats with depleting agents and effects are determined on DAB metabolism, lipid peroxidation and heme oxygenase. Correlations between the effects will be drawn. (2) Standard methods of purification will be used to isolate cytosolic protein(s) which affect P-450-catalyzed metabolism of DAB. The mechanism of the interaction will be investigated by studying the kinetics of DAB metabolism. Health-Related Aspects of Project: Metabolism of xenobiotics may involve activation or detoxication. GSH is a major factor in determining the fate of many xenobiotics and its hepatic level varies with diet and exposure to environmental pollutants. Therefore, understanding GSH control of xenobiotic metabolism provides insight into the potential toxicity of many foreign compounds.